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Herein, an N-heterocyclic carbene (NHC) catalyzed formal [3 + 3] annulation of δ-acetoxy allenoates with 1C,3O-bisnucleophiles for the construction of 4H-(fused)pyrans has been developed. This protocol provides a facile method to synthesize highly functionalized 4H-pyrans and has a broad substrate scope (30 examples, up to 77% yield).
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The SARS-CoV-2 vaccines have been widely used to build an immunologic barrier in the population against the COVID-19 pandemic. However, a newly emerging Omicron variant, including BA.1, BA.1.1, BA.2, and BA.3 sublineages, largely escaped the neutralization of existing neutralizing antibodies (nAbs), even those elicited by three doses of vaccines. Here, we used the Omicron BA.1 RBD as a fourth dose of vaccine to induce potent Omicron-specific nAbs and evaluated the broadly neutralizing activities against SARS-CoV-2 variants. The BA.1-based vaccine was indeed prone to induce a strain-specific antibody response substantially cross-reactive with BA.2 sublineage, and yet triggered broad neutralization against SARS-CoV-2 variants when it was used in the sequential immunization with WT and other variant vaccines. These results demonstrated that the booster of Omicron RBD vaccine could be a rational strategy to enhance the broadly nAb response.
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COVID-19 , Vacinas Virais , Animais , Anticorpos Neutralizantes , Anticorpos Antivirais , COVID-19/prevenção & controle , Vacinas contra COVID-19 , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Pandemias , SARS-CoV-2/genética , Glicoproteína da Espícula de Coronavírus/genéticaRESUMO
OBJECTIVE: Previous study suggested IgG4 levels were associated with the development of Graves' ophthalmopathy (GO). The aims of the present study were to investigate the role of IgG4 levels in glucocorticoid (GC) treatment in GO patients. DESIGN: 69 GO patients were enrolled. Serum thyroid hormones, thyroid antibodies, IgG, IgG4, ophthalmological examinations and orbital MRI were performed. Furthermore, the clinical outcomes (a composite response endpoint including the clinical activity score (CAS), proptosis, vision, intraocular pressure, diplopia and lid width) after high-dose intravenous GC treatment in 32 active moderate-to-severe GO patients were compared. PATIENTS: 69 consecutive patients with GO were asked to participate in the study. 32 of 69 GO patients were treated with high-dose intravenous GCs. MEASUREMENTS: Measurement of serum IgG and IgG4, serum thyroid hormones and thyroid autoantibodies. An overall ophthalmic assessment was performed pretherapy (week 0) and post-therapy (week 12). RESULTS: 33.3% of GO patients (23/69) had elevated IgG4 levels. IgG4 levels were positively correlated with the severity and activity of GO. After GC therapy, IgG4, IgG4/IgG, vision and CAS were significantly improved in GO patients. Patients with high IgG4 levels had a significantly reduced extraocular muscle area (EOMs) and better clinical outcomes than patients with normal IgG4 levels. CONCLUSIONS: Our results suggest a possible subgroup of elevated IgG4 GO patients, with more severe ophthalmopathy and better response to GCs treatment compare with normal IgG4 GO patients.
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Glucocorticoides , Oftalmopatia de Graves , Glucocorticoides/uso terapêutico , Oftalmopatia de Graves/tratamento farmacológico , Humanos , Imunoglobulina G , Imageamento por Ressonância Magnética , Índice de Gravidade de DoençaRESUMO
BACKGROUND: ANGPTL8, an important regulator of lipid metabolism, was recently proven to have additional intracellular and receptor-mediated functions. This study aimed to investigate circulating levels of ANGPTL8 and its potential association with the risk of kidney function decline in a cohort study. METHODS: We analysed 2,311 participants aged 40 years old and older from the China Cardiometabolic Disease and Cancer Cohort (4C) Study. Kidney function decline was defined as an estimated glomerular filtration rate (eGFR) less than 60 mL per minute per 1.73 m2 of body surface area, a decrease in eGFR of ≥ 30% from baseline, chronic kidney disease (CKD)-related hospitalization or death, or end-stage renal disease. The association between baseline ANGPTL8 levels and kidney function decline was assessed using multivariable-adjusted Cox proportional hazards models, and inverse possibility of treatment weight (IPTW) was utilized to prevent overfitting. RESULTS: There were 136 (5.9%) cases of kidney function decline over a median of 3.8 years of follow-up. We found that serum ANGPTL8 levels at baseline were elevated in individuals with kidney function decline compared to those without kidney function decline during follow-up (718.42 ± 378.17 vs. 522.04 ± 283.07 pg/mL, p < 0.001). Compared with the first quartile, multivariable-adjusted hazard ratio (95% confidence intervals [CIs]) for kidney function decline was 2.59 (95% CI, 1.41-4.77) for the fourth ANGPTL8 quartile. Furthermore, compared with patients in the first ANGPTL8 quartile, those in the fourth ANGPTL8 quartile were more likely to report a higher stage of CKD (relative risk: 1.33; 95% CI, 1.01-1.74). The conclusions of the regression analyses were not altered in the IPTW models. Multivariable-adjusted restricted cubic spline analyses suggested a linear relationship of ANGPTL8 with kidney function decline (p for nonlinear trend = 0.66, p for linear trend < 0.001). CONCLUSIONS: Participants with higher circulating ANGPTL8 levels were at increased risk for kidney function decline, highlighting the importance of future studies addressing the pathophysiological role of ANGPTL8 in CKD.
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Proteína 8 Semelhante a Angiopoietina/sangue , Taxa de Filtração Glomerular , Nefropatias/sangue , Rim/fisiopatologia , Hormônios Peptídicos/sangue , Adulto , Idoso , Biomarcadores/sangue , China/epidemiologia , Progressão da Doença , Feminino , Hospitalização , Humanos , Nefropatias/diagnóstico , Nefropatias/mortalidade , Nefropatias/fisiopatologia , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Fatores de Tempo , Regulação para CimaRESUMO
Porcine deltacoronavirus (PDCoV) is an emergent enteropathogenic coronavirus associated with swine diarrhea. Porcine small intestinal epithelial cells (IPEC) are the primary target cells of PDCoV infection in vivo. Here, isobaric tags for relative and absolute quantification (iTRAQ) labeling coupled to liquid chromatography-tandem mass spectrometry (LC-MS/MS) was used to quantitatively identify differentially expressed proteins (DEPs) in PDCoV-infected IPEC-J2 cells. A total of 78 DEPs, including 23 upregulated and 55 downregulated proteins, were identified at 24 h postinfection. The data are available via ProteomeXchange with identifier PXD019975. To ensure reliability of the proteomics data, two randomly selected DEPs, the downregulated anaphase-promoting complex subunit 7 (ANAPC7) and upregulated interferon-induced protein with tetratricopeptide repeats 1 (IFIT1), were verified by real-time PCR and Western blot, and the results of which indicate that the proteomics data were reliable and valid. Bioinformatics analyses, including GO, COG, KEGG, and STRING, further demonstrated that a majority of the DEPs are involved in numerous crucial biological processes and signaling pathways, such as immune system, digestive system, signal transduction, RIG-I-like receptor, mTOR, PI3K-AKT, autophagy, and cell cycle signaling pathways. Altogether, this is the first study on proteomes of PDCoV-infected host cells, which shall provide valuable clues for further investigation of PDCoV pathogenesis.
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Cromatografia Líquida/métodos , Infecções por Coronavirus/metabolismo , Proteoma/análise , Espectrometria de Massas em Tandem/métodos , Animais , Linhagem Celular , Coronavirus , Células Epiteliais/química , Células Epiteliais/metabolismo , Células Epiteliais/virologia , Proteoma/química , Proteoma/metabolismo , Proteômica , SuínosRESUMO
BACKGROUND: Iron overload has been found to be related with various cardiometabolic disorders, like dyslipidemia, metabolic syndrome, and diabetes. The disturbance of the iron status and lipid metabolism can contribute to organ damage such as atherosclerotic plaque growth and instability. An assessment on the associations of iron status with apolipoproteins and lipid ratios would be informative for maintenance of metabolic homeostasis and hinderance of disease progression. Hence, this study aims to establish the relationships of iron status with apolipoproteins and lipid ratios. METHODS: A cross-sectional study of 7540 adult participants from the China Health and Nutrition Survey 2009 was conducted. Logistic regression analyses were used to investigate the relationships between indicators of iron status and the prevalence of unfavorable apolipoprotein profiles. Multivariate linear regression models were constructed to assess the dose-response correlations between serum ferritin and lipid parameters. RESULTS: After adjustment for confounding factors, in both sexes, the subjects in the top quartile of ferritin had the highest prevalence of an elevated apolipoprotein B (men: odds ratio (OR) 1.97, 95% confidence interval (CI) 1.50-2.62; women: OR 2.13, 95% CI 1.53-2.97) and an elevated apolipoprotein B/apolipoprotein A1 ratio (men: OR 2.00, 95% CI 1.50-2.66; women: OR 1.41, 95% CI 1.04-1.92) when compared with individuals in the lowest quartile. Hemoglobin were also independently associated with unfavorable apolipoprotein B and apolipoprotein B/apolipoprotein A1 ratio both in men and women. However, transferrin (men: OR 0.74, 95% CI 0.56-0.99; women: OR 0.73, 95% CI 0.56-0.95) and soluble transferrin receptor (men: OR 0.75, 95% CI 0.57-0.99; women: OR 0.71, 95% CI 0.55-0.91) were found to be negatively associated with a decreased apolipoprotein A1. Moreover, after controlling for potential confounders, the ferritin concentrations were significantly associated with the levels of lipid ratios including TG/HDL-C, non-HDL-C/HDL-C, TC/HDL-C, apoB/apoA1, and LDL-C/HDL-C ratio in men (ß coefficient = 0.147, 0.061, 0.043, 0.038, 0.032, respectively, all P values < 0.001) and in women (ß coefficient = 0.074, 0.034, 0.025, 0.020, 0.018, respectively, all P values < 0.05). CONCLUSIONS: The indicators of iron status are significantly associated with unfavorable apolipoprotein profiles. Serum ferritin concentrations are positively correlated with the levels of lipid ratios. The management on the modifiable iron status and lipid metabolism has a clinical significance. The atherosclerotic lipid profiles of the patients with iron overload deserve special clinical concerns.
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Apolipoproteína A-I/genética , Apolipoproteína B-100/genética , Ferro/sangue , Metabolismo dos Lipídeos/genética , Adulto , Aterosclerose/sangue , Aterosclerose/epidemiologia , Aterosclerose/genética , China/epidemiologia , HDL-Colesterol/sangue , Dislipidemias/sangue , Dislipidemias/epidemiologia , Dislipidemias/genética , Feminino , Ferritinas/sangue , Ferritinas/genética , Hemoglobinas/genética , Humanos , Lipídeos/sangue , Lipídeos/genética , Masculino , Síndrome Metabólica/sangue , Síndrome Metabólica/epidemiologia , Síndrome Metabólica/genética , Pessoa de Meia-Idade , Triglicerídeos/sangueRESUMO
Porcine epidemic diarrhea (PED) caused by porcine epidemic diarrhea virus (PEDV) is a highly contagious intestinal disease, resulting in substantial economic losses to the swine industry worldwide. In this study, three assays, namely a conventional reverse transcription-polymerase chain reaction (RT-PCR), a SYBR Green I real-time RT-PCR and a TaqMan real-time RT-PCR targeting the highly conserved M gene of PEDV, were developed and evaluated. Then, the analytical specificity, sensitivity and reproducibility of these assays were determined and compared. The TaqMan real-time RT-PCR was 100-fold and 10,000-fold more sensitive than that of the SYBR Green I real-time RT-PCR and the conventional RT-PCR, respectively. The analytical sensitivity of TaqMan real-time RT-PCR was 10 copies/µl of target gene and no cross amplification with other viruses tested was observed. With the features of high specificity, sensitivity, and reproducibility, the TaqMan real-time RT-PCR established in this study could be a useful tool for clinical diagnosis, epidemiological surveys and outbreak investigations of PED.
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Infecções por Coronavirus/diagnóstico , Vírus da Diarreia Epidêmica Suína/isolamento & purificação , Reação em Cadeia da Polimerase Via Transcriptase Reversa/métodos , Doenças dos Suínos/diagnóstico , Animais , Benzotiazóis , Infecções por Coronavirus/genética , Infecções por Coronavirus/virologia , Diaminas , Compostos Orgânicos/química , Vírus da Diarreia Epidêmica Suína/genética , Vírus da Diarreia Epidêmica Suína/patogenicidade , Quinolinas , Reação em Cadeia da Polimerase em Tempo Real/métodos , Suínos/virologia , Doenças dos Suínos/genética , Doenças dos Suínos/virologiaRESUMO
Glaucoma, a major cause of blindness worldwide, is a neurodegenerative optic neuropathy in which vision loss is caused by loss of retinal ganglion cells (RGCs). To better define the pathways mediating RGC death and identify targets for the development of neuroprotective drugs, we developed a high-throughput RNA interference screen with primary RGCs and used it to screen the full mouse kinome. The screen identified dual leucine zipper kinase (DLK) as a key neuroprotective target in RGCs. In cultured RGCs, DLK signaling is both necessary and sufficient for cell death. DLK undergoes robust posttranscriptional up-regulation in response to axonal injury in vitro and in vivo. Using a conditional knockout approach, we confirmed that DLK is required for RGC JNK activation and cell death in a rodent model of optic neuropathy. In addition, tozasertib, a small molecule protein kinase inhibitor with activity against DLK, protects RGCs from cell death in rodent glaucoma and traumatic optic neuropathy models. Together, our results establish a previously undescribed drug/drug target combination in glaucoma, identify an early marker of RGC injury, and provide a starting point for the development of more specific neuroprotective DLK inhibitors for the treatment of glaucoma, nonglaucomatous forms of optic neuropathy, and perhaps other CNS neurodegenerations.
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MAP Quinase Quinase Quinases/genética , MAP Quinase Quinase Quinases/fisiologia , Células Ganglionares da Retina/enzimologia , Células Ganglionares da Retina/patologia , Animais , Morte Celular/genética , Morte Celular/fisiologia , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/genética , Sobrevivência Celular/fisiologia , Células Cultivadas , Modelos Animais de Doenças , Regulação para Baixo , Glaucoma/tratamento farmacológico , Glaucoma/etiologia , Humanos , MAP Quinase Quinase Quinases/antagonistas & inibidores , Masculino , Camundongos , Doenças do Nervo Óptico/etiologia , Doenças do Nervo Óptico/patologia , Traumatismos do Nervo Óptico/tratamento farmacológico , Traumatismos do Nervo Óptico/enzimologia , Traumatismos do Nervo Óptico/patologia , Piperazinas/farmacologia , Inibidores de Proteínas Quinases/farmacologia , Interferência de RNA , Ratos , Ratos Wistar , Células Ganglionares da Retina/efeitos dos fármacos , Transdução de Sinais , Regulação para CimaRESUMO
BACKGROUND: To directly compare traditional lipid ratios (total cholesterol [TC]/high density lipoprotein cholesterol [HDL-C], non-HDL-C/HDL-C, low density lipoprotein cholesterol [LDL-C]/HDL-C, and triglycerides [TG]/HDL-C), apolipoprotein B (apoB)/apolipoprotein A-I (apoA-I) ratio, visceral adiposity index (VAI), lipid accumulation product (LAP), and the product of TG and fasting glucose (TyG) for strength and independence as risk factors for insulin resistance (IR). METHODS: We conducted a cross-sectional analysis of 7629 Chinese adults using data from the China Health and Nutrition Survey 2009. RESULTS: For all lipid ratios (traditional lipid ratios and apoB/apoA-I), among both sexes, TG/HDL-C explained the most additional percentage of variation in HOMA-IR (2.9% in men, and 2.3% in women); for all variables of interest, the variability in HOMA-IR explained by VAI and TG/HDL-C were comparable; TyG had the most significant association with HOMA-IR, which explained 9.1% for men and 7.8% for women of the variability in HOMA-IR. Logistic regression analysis showed the similar patterns. Receiver operating characteristic (ROC) curve analysis showed that, among both sexes, TG/HDL-C was a better discriminator of IR than apoB/apoA-I; the area under the ROC curve (AUC) for VAI (0.695 in men and 0.682 in women) was greater than that for TG/HDL-C (AUC 0.665 in men and 0.664 in women); TyG presented the greatest value of AUC (0.709 in men and 0.711 in women). CONCLUSION: The apoB/apoA-I performs no better than any of the traditional lipid ratios in correlating with IR. The TG/HDL-C, VAI and TyG are better markers for early identification of IR individuals.
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Adiposidade/fisiologia , Glucose/metabolismo , Resistência à Insulina , Gordura Intra-Abdominal , Obesidade Abdominal/sangue , Triglicerídeos/sangue , Adulto , Apolipoproteína A-I/sangue , Índice de Massa Corporal , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , RiscoRESUMO
BACKGROUND: Cardiovascular disease (CVD) and obesity are now common among Chinese. We aimed to examine secular trends in the prevalence of low risk profile and to examine whether comparable changes in the prevalence of low risk profile across waist circumference (WC) groups and body mass index (BMI) categories have occurred. METHODS: We used data from the nationwide China Health and Nutrition Survey conducted in 1993, 1997, 2000, 2004, 2006, and 2009. There were 7274, 8368, 9369, 8948, 8786, and 9278 participants included in the analyses across the six study periods. We created an index of low risk factor burden from the following variables: not currently smoking, BMI < 25 kg/m2, WC < 90/80 cm in men/women, untreated systolic/diastolic blood pressure < 120/80 mmHg, and not having been previously diagnosed with diabetes. RESULTS: During the period of 1993-2009, the age-adjusted prevalence of low risk profile decreased from 16.2 to 11.5% among men and from 46.3 to 34.6% among women (both P < 0.001); Similar significant trends were observed in all age groups, rural/urban settings, education groups, WC status and BMI categories. The change in the prevalence of low risk profile was more striking among obese persons (P for interaction terms cohort *BMI were < 0.001). In 2009, 2.0 and 25.6% among central obese men and women had a low risk profile; Of note, was that 0.1 and 0.3% general obese men and women had a low risk profile. CONCLUSIONS: The prevalence of low risk profile declined considerably over the past 17 years in all demographic groups, WC status, and BMI categories. Public health prevention strategies are urgently needed.
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Índice de Massa Corporal , Doenças Cardiovasculares/etiologia , Obesidade/complicações , Circunferência da Cintura , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Povo Asiático , Pressão Sanguínea , China/epidemiologia , Efeitos Psicossociais da Doença , Diabetes Mellitus/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Inquéritos Nutricionais , Obesidade/epidemiologia , Prevalência , Fatores de Risco , Fumar/epidemiologia , Adulto JovemRESUMO
PURPOSE: To report a case of bilateral ciliochoroidal effusion syndrome associated with sildenafil use. CASE REPORT: A 41-year-old male presented with a five-day history of bilateral blurred vision, elevated intraocular pressure, and myopic shift. Ultrasound biomicroscopy radial scans showed closed angles and 360 degrees of ciliochoroidal effusion in both eyes. Anterior segment coherence tomography angiography showed bilateral shallow anterior chamber. Further questioning revealed that the patient had taken sildenafil several times just a few days before symptoms appeared. Since then, the patient stopped dosing sildenafil. After treatment of anti-inflammation and shifting the lens-iris diaphragm posteriorly, the patient's visual acuity improved and intraocular pressure decreased. Follow-up ultrasound biomicroscopy and anterior segment coherence tomography angiography revealed resolution of ciliochoroidal effusion and increase of anterior chamber depth in both eyes. CONCLUSIONS: The patient demonstrated a rare case of sildenafil-induced bilateral ciliochoroidal effusion syndrome. This case report shows that sildenafil should be added to the possible causative agents of ciliochoroidal effusion syndrome.
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The aim of this study is to screen the differentially expressed genes and genes with alternative splicing in PPIA overexpressing cells by transcriptome sequencing. Transcriptome sequencing was performed to identify differentially expressed genes and genes with altered alternative splicing in PPIA overexpressing cells and results were validated by real-time quantitative polymerase chain reaction. The biological function and pathways of those genes were further explored through Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes analyses. A total of 157 significantly upregulated genes and 171 significantly downregulated genes were identified in PPIA overexpressing cells, and the splicing pattern of LHPP, APH1A, BRD1, and ORAI3 was found to be altered. GO analyses showed that the most enriched GO terms of the 157 upregulated genes included extracellular region, protein binding, and metal ion, and the most enriched GO terms of the 171 downregulated genes included binding neuron projection, protein binding, and endoplasmic reticulum unfolded protein response. Kyoto Encyclopedia of Genes and Genomes analyses showed that the 157 upregulated genes were mainly enriched in gastric acid secretion, Mitogen-activated protein kinase signaling pathway, etc, and the 171 downregulated genes were mainly enriched in transcriptional misregulation in cancer, Tumor necrosis factor signaling pathway, etc. The overexpression of PPIA in human umbilical vein endothelial cells causes changes in the expression of downstream genes and induces alternative splicing in multiple genes. PPIA alters the expression or the alternative splicing pattern of downstream genes, leading to pathogenesis of vascular endothelial injury by high glucose mediated through CyPA.
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Células Endoteliais da Veia Umbilical Humana , Humanos , Processamento Alternativo , Regulação para Cima , Perfilação da Expressão Gênica/métodos , Regulação da Expressão Gênica , Transcriptoma , Regulação para Baixo , Reação em Cadeia da Polimerase em Tempo Real , Ontologia Genética , Expressão Gênica/genéticaRESUMO
This work investigated the effect of oscillation-assisted hydrothermal process on extraction of caffeic acid and ferulic acid from sorghum straws. The results showed that the oscillation-assisted hydrothermal process efficiently improved extraction of caffeic acid and ferulic acid. The oscillation-assisted hydrothermal process resulted in the extraction rates of 1275.48 and 1822.64 mg/L.h for caffeic acid and ferulic acid, respectively. Moreover, the oscillation-assisted hydrothermal process exerted destructive effects on hemicellulose, lignin and the amorphous regions of cellulose, contributing to the release of caffeic acid and ferulic acid in pretreated sorghum straws. The scavenging activities for hydroxyl, 1,1-diphenyl-2-picrylhydrazyl and 2,2'-azino-bis-3-ethylbenzthiazoline-6-sulfonic acid radicals of the caffeic acid and ferulic acid extracts obtained by the oscillation-assisted hydrothermal process were determined to be 83.69 %, 84.17 % and 88.45 %, respectively.
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Sorghum , Ácidos Cafeicos , Ácidos CumáricosRESUMO
Sulfur-containing gases are main sources of landfill odors, which has become a big issue for pollution to environment and human health. Biocover is promising for treating landfill odors, with advantages of durability and environmental friendliness. In this study, charcoal sludge compost was utilized as the main effective component of a novel alternative landfill cover and the in situ control of sulfur-containing odors from municipal solid waste landfilling process was simulated under nine different operating conditions. Results showed that five sulfur-containing odors (hydrogen sulfide, H2S; methyl mercaptan, CH3SH; dimethyl sulfide, CH3SCH3; ethylmercaptan, CH3CH2SH; carbon disulfide, CS2) were monitored and removed by the biocover, with the highest removal efficiencies of 77.18% for H2S, 87.36% for CH3SH, and 92.19% for CH3SCH3 in reactor 8#, and 95.94% for CH3CH2SH and 94.44% for CS2 in reactor 3#. The orthogonal experiment showed that the factors influencing the removal efficiencies of sulfur-containing odors were ranked from high to low as follows: temperature > weight ratio > humidity content. The combination of parameters of 20% weight ratio, 25°C temperature, and 30% water content was more recommended based on the consideration of the removal efficiencies and economic benefits. The mechanisms of sulfur conversion inside biocover were analyzed. Most organic sulfur was firstly degraded to reduced sulfides or element sulfur, and then oxidized to sulfate which could be stable in the layer as the final state. In this process, sulfur-oxidizing bacteria play a great role, and the distribution of them in reactor 1#, 5#, and 8# was specifically monitored. Bradyrhizobiaceae and Rhodospirillaceae were the dominant species which can utilize sulfide as substance to produce sulfate and element sulfur, respectively. Based on the results of OUTs, the biodiversity of these sulfur-oxidizing bacteria, these microorganisms, was demonstrated to be affected by the different parameters. These results indicate that the novel alternative landfill cover modified with bamboo charcoal compost is effective in removing sulfur odors from landfills. Meanwhile, the findings have direct implications for addressing landfill odor problems through parameter adjustment.
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Sulfeto de Hidrogênio , Odorantes , Humanos , Carvão Vegetal/metabolismo , Sulfeto de Hidrogênio/metabolismo , Enxofre/metabolismo , Instalações de Eliminação de Resíduos , Óxidos de Enxofre , Bactérias/metabolismo , Sulfatos/metabolismoRESUMO
Genome-wide association study (GWAS) has identified genetic variants in the promoter region of the high temperature requirement factor A1 (HTRA1) gene associated with age-related macular degeneration (AMD). As a secreted serine protease, HTRA1 has been reported to interact with members of the transforming growth factor-ß (TGF-ß) family and regulate their signaling pathways. Growth differentiation factor 6 (GDF6), a member of the TGF-ß family, is involved in ectoderm patterning and eye development. Mutations in GDF6 have been associated with abnormal eye development that may result in microphthalmia and anophthalmia. In this report, we identified a single nucleotide polymorphism (SNP) rs6982567 A/G near the GDF6 gene that is significantly associated with AMD (p value = 3.54 × 10(-8)). We demonstrated that the GDF6 AMD risk allele (rs6982567 A) is associated with decreased expression of the GDF6 and increased expression of HTRA1. Similarly, the HTRA1 AMD risk allele (rs10490924 T) is associated with decreased GDF6 and increased HTRA1 expression. We observed decreased vascular development in the retina and significant up-regulation of GDF6 gene in the RPE layer, retinal and brain tissues in HTRA1 knock-out (htra1(-/-)) mice as compared with the wild-type counterparts. Furthermore, we showed enhanced SMAD signaling in htra1(-/-) mice. Our data suggests a critical role of HTRA1 in the regulation of angiogenesis via TGF-ß signaling and identified GDF6 as a novel disease gene for AMD.
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Fator 6 de Diferenciação de Crescimento/biossíntese , Degeneração Macular/metabolismo , Neovascularização Patológica/metabolismo , Polimorfismo de Nucleotídeo Único , Serina Endopeptidases/biossíntese , Idoso , Alelos , Animais , Estudos de Coortes , Feminino , Regulação da Expressão Gênica/genética , Fator 6 de Diferenciação de Crescimento/genética , Serina Peptidase 1 de Requerimento de Alta Temperatura A , Humanos , Degeneração Macular/genética , Degeneração Macular/patologia , Masculino , Camundongos , Camundongos Knockout , Pessoa de Meia-Idade , Neovascularização Patológica/genética , Neovascularização Patológica/patologia , Retina/metabolismo , Retina/patologia , Fatores de Risco , Serina Endopeptidases/genética , Transdução de Sinais/genética , Proteínas Smad/genética , Proteínas Smad/metabolismoRESUMO
We estimated the key molecules related to Type 2 diabetes mellitus (T2DM) in adipose, liver, and muscle tissues, from nonobese diabetic Goto-Kakizaki (GK) rats and their Wistar controls, by computationally analyzing the expression profiles in open source data. With the aid of information from previous reports, Rev-erbα in adipose tissue emerged as one of the most plausible candidates. Here, in animal models, including GK rats surgically treated to ameliorate T2DM, we examined the association of Rev-erbα in adipose tissue with T2DM progression. After analyses of the Rev-erbα mRNA expression in the adipose tissue of our animal models, we compared the Rev-erbα protein expression levels in the adipose, liver, and muscle tissues of GK and Wistar controls at the ages of 1 mo (M), 3M, and 6M. The Rev-erbα protein levels in adipose tissue showed a distinctive pattern, with the negative correlation of an increasing trend in GK rats, and a decreasing trend in Wistar rats during aging, from those in liver and muscle tissues. Moreover, dysregulation of the circadian Rev-erbα expression in the adipose tissue of 6-mo-old GK rats was also observed. In particular, we ameliorated T2DM in GK rats by gastric bypass surgery, and revealed that T2DM amelioration in diabetic GK rats was associated with improved circadian Rev-erbα expression, in a comparison between the surgically treated and untreated GK rats. The roles of Rev-erbα in adipose tissue were further investigated by observations of Rev-erbα-related molecules, with reference to previous reports.
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Tecido Adiposo/metabolismo , Ritmo Circadiano/fisiologia , Diabetes Mellitus Tipo 2/metabolismo , Derivação Gástrica , Membro 1 do Grupo D da Subfamília 1 de Receptores Nucleares/metabolismo , Obesidade/metabolismo , Tecido Adiposo/fisiopatologia , Animais , Peso Corporal/fisiologia , Diabetes Mellitus Tipo 2/fisiopatologia , Diabetes Mellitus Tipo 2/cirurgia , Progressão da Doença , Fígado/metabolismo , Fígado/fisiopatologia , Masculino , Músculo Esquelético/metabolismo , Membro 1 do Grupo D da Subfamília 1 de Receptores Nucleares/genética , Obesidade/fisiopatologia , Obesidade/cirurgia , Ratos , Ratos WistarRESUMO
OBJECTIVE: To characterize the plasma renin activity (PRA) and plasma aldosterone concentration (PAC) and aldosterone/renin ratio (ARR) in patients with aldosterone-producing adenoma (APA). METHODS: We retrospectively analysed the data of PRA, PAC and ARR from 80 patients with APA, 70 patients with essential hypertension (EH) and 26 individuals with normal blood pressure (NBP). Patients with hypertension were further divided into taking anti-hypertensive drug group (D) and non drug treatment group (ND). All participants received at least one following tests:ARR screening test, supine-upright position test and saline load test.Receiver-operating characteristic (ROC) analysis was used for exploring the best cut-off value of ARR and low PRA. RESULTS: The median and percentages of PRA (ng×ml(-1)×h(-1), 1 ng×ml(-1)×h(-1) = 1 µg×L(-1)×h(-1)), PAC (ng/dl, 1 ng/dl = 27.7 pmol/L) and ARR (ng×dl(-1)/ng×ml(-1)×h(-1)) between NBP and EH (ND) groups showed no differences.Over 90% supine PRA ≥ 0.52 and 100% upright PRA ≥ 0.52 in the above two groups. On the contrary, 90% APA (ND) patients upright PRA <0.52. The lowest supine and upright ARR in APA (ND) patients was ≥ 24.2 and ≥ 37.5 respectively. ROC analysis suggested that the best screening cut-off values for APA were supine ARR ≥ 26.0, upright ARR ≥ 37.0; and low PRA cut-off value for APA were supine PRA <0.50 and upright PRA < 0.63 respectively. The sensitivity and specificity for APA diagnosis were about 88.2% and 61.5% when PAC ≥ 10.0 after saline load test. CONCLUSIONS: The distinguishing features of PRA, PAC and ARR can be used as a diagnostic indexs for the exclusive diagnosis of APA in various clinical tests. And low PRA cut-off values exist in APA patients.
Assuntos
Neoplasias das Glândulas Suprarrenais/sangue , Neoplasias das Glândulas Suprarrenais/diagnóstico , Aldosterona/sangue , Hiperaldosteronismo/sangue , Renina/sangue , Neoplasias das Glândulas Suprarrenais/patologia , Adulto , Estudos de Casos e Controles , Hipertensão Essencial , Feminino , Humanos , Hiperaldosteronismo/patologia , Hipertensão/sangue , Hipertensão/tratamento farmacológico , Hipertensão/patologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto JovemRESUMO
With the ongoing COVID-19 pandemic and the emergence of various SARS-CoV-2 variants, a comprehensive evaluation of long-term efficacy of antibody response in convalescent individuals is urgently needed. Several longitudinal studies had reported the antibody dynamics after SARS-CoV-2 acute infection, but the follow-up was mostly limited to 1 year or 18 months at the maximum. In this study, we investigated the durability, potency, and susceptibility to immune evasion of SARS-CoV-2-specific antibody in COVID-19 convalescents for 2 years after discharge. These results showed the persistent antibody-dependent immunity could protect against the WT and Delta variant to some extent. However, the Omicron variants (BA.1, BA.2, and BA.4/5) largely escaped this preexisting immunity in recovered individuals. Furthermore, we revealed that inactivated vaccines (BBIBP-CorV, CoronaVac, or KCONVAC) could improve the plasma neutralization and help to maintain the broadly neutralizing antibodies at a certain level. Notably, with the time-dependent decline of antibody, 1-dose or 2-dose vaccination strategy seemed not to be enough to provide immune protection against the emerging variants. Overall, these results facilitated our understanding of SARS-CoV-2-induced antibody memory, contributing to the development of immunization strategy against SARS-CoV-2 variants for such a large number of COVID-19 survivors.
Assuntos
COVID-19 , SARS-CoV-2 , Humanos , SARS-CoV-2/genética , COVID-19/prevenção & controle , Formação de Anticorpos , Pandemias , Anticorpos Antivirais , Vacinação , Anticorpos NeutralizantesRESUMO
Aims: Our aim was to investigate the prevalence, incidence, and persistence of visual impairment (VI) and their correlates among the Chinese population with diabetes mellitus (DM) over 3 years. Materials and methods: The China Health and Retirement Longitudinal Survey is the first nationally representative longitudinal survey of the Chinese population. A cross-sectional analysis of prevalent VI in 2015 consisted of 2,173 participants with DM. A longitudinal observation of incident and persistent VI consisted of 1,633 participants from 2015 to 2018. Risk factors of VI were identified via univariate and multivariate logistic regression analyses. Results: Among our study population with DM, 11.8% reported VI in 2015, 4.5% had persistent VI from 2015 to 2018, and 8.9% developed VI in 2018. Factors identified to be correlated to VI (p < 0.05) were older age, being a woman, lower educational attainment, living in a rural area, application of DM medication and non-pharmacological treatment, receiving DM-related tests, use of spectacles, and poorer health status. Conclusion: This most recent national data provides a baseline for future public health initiatives on VI among the Chinese population with DM. With multiple risk factors identified, these could provide concurrent targets for various public health strategies and interventions with the aim of reducing the burden of VI among the population with DM in China.
Assuntos
Diabetes Mellitus , População do Leste Asiático , Transtornos da Visão , Feminino , Humanos , Estudos Transversais , Diabetes Mellitus/epidemiologia , Diabetes Mellitus/terapia , População do Leste Asiático/etnologia , População do Leste Asiático/estatística & dados numéricos , Incidência , Prevalência , Autorrelato , Transtornos da Visão/epidemiologia , Transtornos da Visão/etiologia , Complicações do Diabetes/complicações , Complicações do Diabetes/etnologia , China/epidemiologia , MasculinoRESUMO
[This corrects the article DOI: 10.3389/fpubh.2023.978457.].